12-10-21 - Responses to Cell and Tissue Injury Flashcards
What are the 2 main events that occur to cells during sub-lethal injury?
What do these changes reflect? Are these changes reversible?
What are 2 events that occur to the cell over a longer period of time?
- Because of sublethal injury there are 2 reversible changes
- Hydropic change/oncosis – excess water moves into the cell, reflecting the membrane losing its integrity
- Fatty change/steatosis – Fat accumulation which reflects dysregulation of intercellular metabolism
- These events that occur as a result of sublethal injury are reversible
- 2 events that occur over a longer period:
- Atrophy – cell becomes smaller with less energy reserves and function
- Autophagy – Cell begins to degrade part of itself to become a smaller cell
- What are the 3 factors that determine the response to injury?
- Response to injury is determined by the nature of the injury:
- Acute vs chronic – different set of effects due to acute being sudden onset and chronic being repeated
- Mild vs severe
- Cell type affected – damage to skin cell is easier to deal with as it constantly regenerates. Brain cells can not be replaced.
What are the 2 stages of lethal injury?
What occurs during the 2nd stage?
What is this known as?
- Lethal injury has a reversible stage follow by an irreversible stage.
- During the irreversible stage, there is a total loss of membrane integrity
- Water floods the cell, damaging organelles, such as lysosomes
- The hydrolytic enzymes within lysosomes spill out and cause the cell to start digesting itself (autophagy)
- The nucleus condenses and becomes non-functional
- This is known as necrosis – a catastrophic collapse of cell viability
What is necrosis?
What type of process is it?
What tissues does it target?
What does it evoke?
- Necrosis is the death of tissues following bioenergetic failure and loss of plasma membrane integrity
- Necrosis is a pathological process – an organic process occurring as a consequence of disease (not regular (physiology)
- Necrosis often effects solid masses of tissues, as the factors that cause necrosis affect a large number of cells e.g poison, trauma, cut off blood supply
- Necrosis evokes an inflammatory response
What happens during the 6 types of necrosis?
coagulative
colliquative
caseous
gangrenous
fibrinoid
fat
- 6 types of necrosis:
- Coagulative
- The most common type of necrosis
- Involves coagulation of cellular proteins to form a goo
- Initially firm, but later soft
- Colliquative
- Dead area is liquified due to proteolysis dominating over coagulation
- Forms cystic spaces
- Occurs in the brain
- Caseous
- pale, yellow, semi-solid material forms
- occurs in TB
- Gangrenous
- Necrosis with putrefaction (process of decay or rotting)
- due to lack of blood flow, or serious bacterial infection
- There are wet and dry forms, with the gas gangrene caused due to bacterium Clostridium perfringens
- Fibrinoid
- Occurs when antibody-antigen complexes are deposited in walls of blood vessels with fibrin
- Results in the insudation (accumulation of substance derived from blood) of plasma proteins in the blood vessel wall and activation of fibrin coagulation
- Most often associated with accelerated severe hypertension.
- Fat necrosis
- Can occur anywhere on the body, but the most common place is the breast.
What is apoptosis?
What does it target and why?
How does apoptosis occur?
What does it not cause?
Where are 3 times apoptosis used and why?
- Apoptosis is controlled cell death that removes a cell discreetly
- Apoptosis takes out individual cells rather than groups of tissues in order to preserve function as much as possible.
- The single cell fragments and is cleared up by a professional phagocyte (e.x macrophage)
- The fragments are still membrane bound, meaning this does not trigger inflammatory responses.
- In embryology, apoptosis forms the lumens of tubes, and the space in between fingers
- Apoptosis is used to cause cell death and prevent tumours
- Apoptosis can also destroy cells that are infected in order to prevent the spread of infection
What is the difference between programmed cell death and apoptosis?
How are they linked together?
What is an example of when apoptosis does not occur?
- Programmed cell death is the intent, apoptosis is the actual process of cell death
- Programmed cell death occurs through apoptosis most of the time
- Programmed cell death occurs via apoptosis at the end of the cells life when it has served its purpose.
- Apoptosis can occur in a cell as a consequence for getting infected, or getting its DNA damaged. This was not originally planned for that cell.
- All programmed cell death is apoptosis, but not all apoptosis is PBC
- Apoptosis does not occur in keratinocytes
- Keratinocytes have died, and are part of the stratum corneum layer of the epidermis, but they haven’t been totally destroyed.
What is proptosis?
What is it associated with?
- Proptosis is partly apoptosis, but then necrosis
- Associated with salmonella infection
What are the 3 divisions of cells in regards to regeneration?
What is the difference between healing and repair?
- Cells can be divided into 3 populations:
- Labile – cells that regenerate frequently e.g skin cells, blood cells, gut cells
- Stable – cells that don’t constantly turn over, but can still replace cells effectively e.g liver cells and kidney tubule cells
- Permanent populations – don’t like growing at all e.g. skeletal muscles, neurones (most neurones can’t be replaced)
- Healing is restoration with no, or minimal, effects left over.
- Repair is the second-best option to healing
- Repair is needed when there is a loss of tissue
- Repair is healing, but there may be some residual effects, such as scarring instead of all the tissue being replaced.
What are the usual sequelae of acute inflammation?
What can cause it to take difference routes?
- Acute inflammation typically ends in resolution
- If there is excess exudate, this can lead to suppuration, which can cause the discharge of pus, and eventually leads to repair and organisation
- If there is excessive necrosis (dead tissue), this can lead to repair and organisation, which can cause fibrosis (thickening or scarring of the tissue)
- If the causal agent Is persistent, this can cause chronic inflammation, which can lead to fibrosis)
When does healing by first and second intention occur?
How does healing by first intention occur?
How does healing by second intention occur?
What are the differences in healing by first and second intention?
- Healing by first intention is the healing occurs when there is a clean laceration, or a surgical incision closed with primary sutures.
- Healing by first intention process:
- Incision
- Weak fibrin joint forms
- Strong collagen joins together
- Healing by second intention is healing that occurs in heavily traumatized, contaminated wounds that may have a prolonged treatment phase.
- Healing by second intention process:
- Loss of tissue
- Organisation (acute inflammatory phase) - Granulation tissue forms, bleeding starts and new capillaries sprout, and collagen is produced
- Early fibrous scar forms – proliferative cells grow across wound bed to regenerate the tissue. Scar is formed from parallel bundles of collagen fibres
- Scar contraction – granulation tissue contracts to make wound size smaller.
- In healing by first intention there is:
- Minimal tissue injury/necrosis
- Minimum bleeding
- Minimum inflammation
- Minimum scarring
- In healing by second intention there are more of these different factors
What is organisation?
What does organisation involve?
What are 3 factors that favour organisation?
- Organisation is the replacement of destroyed tissue by granulation tissue, which leads to fibrosis (fibrous tissue, composed of parallel bundles of collagen)
- Organisation involves:
- Formation of granulation tissues
- Removal of dead tissue by phagocytosis
- Wound contraction and scarring
- Factors that favour organisation:
- Large amounts of fibrin (used in wound healing - clotting factor that helps wound contract)
- Substantial necrosis
- Exudate and debris cannot be removed or discharged
When is granulation tissue formed?
What does it replace?
What does it contain?
What regulates this?
- When inflammatory exudate cannot be cleared away properly, it is replaced by granulation tissue containing:
- Capillaries
- Macrophages
- Fibroblasts
- Collagen
- This is regulated by growth factors: EGF, FGF, TNF
What are factors that favour resolution from acute inflammation?
- Minimal cell death and tissue damage
- Occurrence in an organ or tissue with regenerative capability, such as the liver
- Rapid destruction of the causal agent
- Rapid removal of fluid and debris by good local vascular drainage
How long do fractures take to heal?
What does a fracture lead to?
What is the process of fracture healing?
- Fractures take 2-4 weeks to heal, depending on age, severity and position of fracture
- A fracture leads to inflammation and an increase in blood flow
- This leads to callus formation – osteoblasts quickly form woven bone to bridge the gap, which is weak as the collagen fibres are not organised or mineralised well.
- Lamellar bone is then laid down – collagen is now organised in regular sheets to give strength and resilience
What does necrosis in the bone cause?
What is the process of the bone healing from this?
RRR
Necrosis in the bone leads to organisation
This leads to fibrous tissue called callous forming
Osteoblasts cells get into the fibrous tissue and lay down osteoid, which become calcified
In time, the bone is remodelled by osteoblasts and osteoclasts to become completely regenerated.
What do scars provides?
Why might scars cause a problem?
What is an example?
- Scars provide a permanent patch which allows surrounding tissue to function
- Scars may cause cosmetic or functional problems
- An example of a functional problem is a healed myocardial infarct (heart attack)
- At 7-10 days after a heart attack, sufferers are at greatest risk for rupture
- At this time, there is removal of dead muscle fibres, which are replaced by soft granulation tissue before collagen is formed.
- This may not be strong enough when the heart is pumping, which may cause rupture
What is cirrhosis?
What causes cirrhosis in the liver in terms of regeneration?
- Cirrhosis is scarring of the liver.
- In the liver, Cirrhosis is caused regeneration and scarring occurring together
- Although the liver has the capacity to regenerate, because the injury is chronic, the necrosis is chronic, and the inflammation is chronic.
- There is constant damage being done to the liver, without the opportunity to completely heal.
- Regeneration has capacity, and the liver will eventually no longer heal.
What are the 3 different types of abnormal wound formations?
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